Method for predicting responsiveness to cancer treatment using p300-inhibiting compound

Abstract

It has been found that CBP and p300 are in the relationship of synthetic lethality, and treatment inhibiting p300 is a promising approach for the treatment of CBP-mutated cancer. It has also been revealed that this therapeutic strategy achieves efficient treatment based on companion diagnostics because a p300 inhibitor can be administered to a cancer patient selected with functional suppression of CBP as an index.

The invention claimed is: 
     
       1. A method for improving the response rate of the treatment of cancer, comprising using a biological sample derived from a cancer patient, detecting the presence of a CBP mutation contained in the biological sample, determining the patient is responsive to the treatment of cancer with a compound inhibiting p300, and treating the patient by a method consisting of administrating to the patient an amount of a compound inhibiting p300 and a pharmaceutically acceptable carrier effective to suppress the growth of cancer cells, wherein the mutation is a homozygous CBP deletion, a nonsense mutation, or one of the mutations Asn83Thr, Ser893Leu, Arg1446Cys, Trp1472Cys, Asn2175Ser, Glu1835Stop, Asn2111Ser, Leu551Ile, Gly1411Glu, or Ala2044Gly. 
     
     
       2. A method for improving the response rate of the treatment of cancer, comprising using a biological sample derived from a cancer patient, detecting the presence of a CBP mutation in the biological sample, selecting the patient as the candidate for the treatment of cancer with a compound inhibiting p300, and treating the patient by a method consisting of administrating to the patient an amount of a compound inhibiting p300 and a pharmaceutically acceptable carrier effective to suppress the growth of cancer cells, wherein the mutation is a homozygous CBP deletion, a nonsense mutation, or one of the mutations Asn83Thr, Ser893Leu, Arg1446Cys, Trp1472Cys, Asn2175Ser, Glu1835Stop, Asn2111Ser, Leu551Ile, Gly1411Glu, or Ala2044Gly. 
     
     
       3. A method for treating cancer having functional suppression of CBP, comprising using a biological sample derived from a cancer patient, detecting the presence of functional suppression of CBP contained in the biological sample, and treating the patient by a method consisting of administering to the patient an amount of a compound inhibiting p300 and a pharmaceutically acceptable carrier effective to suppress the growth of cancer cells, and suppressing the growth of the cancer cells to the patient. 
     
     
       4. The method of  claim 1 , wherein detecting the presence of a CBP mutation contained in the biological sample comprises contacting the biological sample with a reagent comprising any of the following molecules (a) to (c) as an active ingredient:
 (a) an oligonucleotide primer specifically binding to the CBP gene, 
 (b) an oligonucleotide probe specifically binding to the CBP gene, and 
 (c) an antibody specifically binding to the CBP protein. 
 
     
     
       5. The method of  claim 2 , wherein detecting the presence of a CBP mutation contained in the biological sample comprises contacting the biological sample with a reagent comprising any of the following molecules (a) to (c) as an active ingredient:
 (a) an oligonucleotide primer specifically binding to the CBP gene, 
 (b) an oligonucleotide probe specifically binding to the CBP gene, and 
 (c) an antibody specifically binding to the CBP protein. 
 
     
     
       6. The method of  claim 3 , wherein detecting the presence of functional suppression of CBP contained in the biological sample comprises contacting the biological sample with a reagent comprising any of the following molecules (a) to (c) as an active ingredient:
 (a) an oligonucleotide primer specifically binding to the CBP gene, 
 (b) an oligonucleotide probe specifically binding to the CBP gene, and 
 (c) an antibody specifically binding to the CBP protein. 
 
     
     
       7. The method of  claim 3 , wherein detecting the presence of functional suppression of CBP contained in the biological sample comprises detecting the presence of a CBP mutation contained in the biological sample, wherein the mutation is a homozygous CBP deletion, a nonsense mutation, or one of the mutations Asn83Thr, Ser893Leu, Arg1446Cys, Trp1472Cys, Asn2175Ser, Glu1835Stop, Asn2111Ser, Leu551Ile, Gly1411Glu, or Ala2044Gly. 
     
     
       8. The method of  claim 3 , wherein the cancer having functional suppression of CBP is lung cancer, bladder cancer, lymphoma, or adenoid cystic cancer. 
     
     
       9. A method for treating a cancer patient, wherein the patient has been determined to have functional suppression of CBP, comprising treating the patient by a method consisting of administering to the patient an amount of a compound inhibiting p300 and a pharmaceutically acceptable carrier effective to suppress the growth of cancer cells, and suppressing the growth of the cancer cells. 
     
     
       10. The method of  claim 9 , wherein the presence of functional suppression of CBP is determined by using a biological sample derived from the patient, contacting the biological sample with a reagent comprising any of the following molecules (a) to (c) as an active ingredient:
 (a) an oligonucleotide primer specifically binding to the CBP gene, 
 (b) an oligonucleotide probe specifically binding to the CBP gene, and 
 (c) an antibody specifically binding to the CBP, and 
 detecting the presence of functional suppression of CBP in the biological sample. 
 
     
     
       11. The method of  claim 9 , wherein the presence of functional suppression of CBP is determined by detecting the presence of a CBP mutation contained in a biological sample derived from the patient, wherein the mutation is a homozygous CBP deletion, a nonsense mutation, or one of the mutations Asn83Thr, Ser893Leu, Arg1446Cys, Trp1472Cys, Asn2175Ser, Glu1835Stop, Asn2111 Ser, Leu551Ile, Gly1411Glu, or Ala2044Gly. 
     
     
       12. The method of  claim 9 , wherein the patient is affected by lung cancer, bladder cancer, lymphoma, or adenoid cystic cancer.